This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tsai, L. N.
Right arrow Articles by Crowe, D. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tsai, L. N.
Right arrow Articles by Crowe, D. L.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2008, p. 4240-4250, Vol. 28, No. 13
0270-7306/08/$08.00+0     doi:10.1128/MCB.01489-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Extracellular Signals Regulate Rapid Coactivator Recruitment at AP-1 Sites by Altered Phosphorylation of both CREB Binding Protein and c-jun{triangledown}

Linh N. Tsai, Tony K. S. Ku, Nader K. Salib, and David L. Crowe*

University of Illinois Cancer Center, 801 S. Paulina Street, Room 530C, MC860, Chicago, Illinois 60612

Received 18 August 2007/ Returned for modification 27 December 2007/ Accepted 16 April 2008

Retinoic acid (RA) inhibits matrix metalloproteinase 9 (MMP-9) expression due to AP-1 inhibition resulting from retinoic acid receptors (RARs) competing for limiting amounts of coactivator proteins. However, given the rapid kinetics of MMP-9 transcription, it seems unlikely that these interactions can be explained passively. Our previous studies indicated that coactivator and transcription factor phosphorylation may allow for rapid regulation of MMP-9 expression. In the present study we tested this hypothesis directly. CREB binding protein (CBP) and p300/CBP-associated factor (PCAF) were displaced from transcription factor binding sites on the MMP-9 promoter within minutes of RA treatment. The RAR interaction domains of CBP and PCAF were not required for this displacement. RA and epidermal growth factor had opposing effects on phosphorylation of CBP by extracellular signal-regulated kinase 1 that correlated with altered CBP occupancy of AP-1 sites and differential MMP-9 promoter activation. We identified a novel phosphorylation site in the CBP carboxyl terminus that mediated association with AP-1 sites in the MMP-9 promoter. Inhibition of c-jun phosphorylation displaced PCAF from AP-1 sites and reduced promoter activity. Phosphorylation deficient c-jun was less able to recruit PCAF to AP-1 sites. We also demonstrated novel interactions between coactivators and AP-1 proteins. We propose that extracellular signal-mediated coactivator exchange at AP-1 sites is mediated via protein kinase pathways.

* Corresponding author. Mailing address: University of Illinois Cancer Center, 801 S. Paulina Street, Room 530C, MC860, Chicago, IL 60612. Phone: (312) 996-9488. Fax: (312) 413-1604. E-mail: dlcrowe{at}uic.edu

{triangledown} Published ahead of print on 28 April 2008.

Molecular and Cellular Biology, July 2008, p. 4240-4250, Vol. 28, No. 13
0270-7306/08/$08.00+0     doi:10.1128/MCB.01489-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»